A few days ago, ICH released a position paper inviting public review and comment on a Reflection Paper on Good Clinical Practice (GCP) “Renovation” (The closing date for public comment is 11-Mar-17).
The scope of the proposed renovation includes the current E8 “General Considerations for Clinical Trials” and further revision to the E6 “Guideline for Good Clinical Practice” , which is already undergoing modernization with the recent production of an addendum.
ICH believes that the proposal outlined in this reflection paper would largely address concerns recently expressed by some research organizations and an international consortium of health researchers about the addendum.
Renovation of ICH E8:
E8 “General Considerations for Clinical Trials” was finished in 1997 and has not been updated subsequently. The revision will clearly focus on data quality and will incorporate the most current concepts about it.
Renovation of ICH E6:
ICH is also proposing a subsequent renovation of the current ICH E6 guideline that would preserve a key role for the current focus on traditional interventional trials conducted in a clinical trial setting while also addressing the other types of data sources or decision contexts.
Probably the main point in the renovation of ICH E6 is the references it will now include on other guidelines or documents:
Logically, the renovated E6 would refer to the proposed-to-be-revised E8 guideline for a more comprehensive discussion of study quality considerations and relevant discussion and guidance in other ICH E guidelines (The current ICH E6(R2) mentions only 2 other ICH guidelines: 3 times the ICH E2A “ICH Guideline for Clinical Safety Data Management Definitions and Standards for Expedited Reporting”, and one time the ICH E3 “Structure and Content of Clinical Study Reports” for the Section 9.6 on Data Quality Assurance).
More importantly, it will also refer to a number of non-ICH reference documents from FDA, EMA & MHLW:
• FDA Guidance to industry: Oversight of Clinical Investigations—A Risk-Based Approach to Monitoring
• EMA Reflection paper on risk based quality management in clinical trials
• MHLW administrative notice on Basic Principles of Riskbased Monitoring
Key addition to the current ICH E6(R2), will be a set of proposed annexes that would be developed:
Each annex would address in more detail a particular type of study and/or data source to which E6 could be applied, and provide a more detailed workup of the Critical-to-Quality (CTQ) factors that should be considered :
Annex 1: Traditional Interventional Trials of investigational unapproved or approved Drugs
Annex 2: Non-Traditional Interventional Trials and/or data sources.
Annex 3: Non-Traditional Trial Designs.
Proposed Plan for “Renovation” Work is presented as Guideline effort 1 to 5:
First effort would focus on modernization of E8. Plan is to potentially start in late 2017 or in 2018.
For renovation of ICH E6, First step (Develop new ICH E6 Overarching Principles guideline) may start after the ICH E8 reaches at least Step 2b (Adoption of draft Guideline by Regulatory Members). Following efforts will be on Annexes development as a staggered approach.
Develop E6 Annex 1: This work would start after the work on the ICH E6 Overarching Principles has reached at least Step 2b.
Develop ICH E6 Annex 2: This work would be expected to start after the Annex 1 had reached at least Step 2b.
Develop ICH E6 Annex 3: This work would be expected to start after the Annex 2 had reached at least Step 2b.
It is also being proposed that ICH incorporate a process of engagement in recognition of the considerable stake and significant GCP expertise of parties outside ICH in the academic research community.
The process includes seeking stakeholder comment on this overall GCP Renovation proposal, on the Concept Paper and Business Plan associated with the Guideline efforts, and to hold meetings with public stakeholders at one or more points in the proposed guideline development.
As the current reflection does not provide a target date for ICH E8 renovation step 2b, it is difficult to establish a planning of the subsequent ICH E6 renovation steps, and the finalization of this ICH GCP renovation.
Focus is currently on achieving step 5 for the E6(R2). So far, Europe seems to lead the implementation period with the document finally approved by CHMP in Dec 16, and coming into effect on 14 Jun 2017.